Correlation between the molecular structure of N-alkylureas and N-alkylthioureas and their teratogenic properties.
Eleven urea compounds were administered individually as a single oral dose to rats either on day 12 or 14 and to mice on day 10 of pregnancy. 1-Methylurea and 1-ethylurea were not teratogenic in either of the animal species. Administration of 1-methylthiourea and 1-ethylthiourea, however, resulted in high incidences of malformations in the rat but not in the mouse fetuses. The types of malformation were similar to those produced by the known teratogen ethylenethiourea. Methylated ureas such as 1,3-dimethylurea, 1,3-dimethylthiourea, 1,1,3,3-tetramethylurea, and 1,1,3,3-tetramethylthiourea were fetotoxic and produced malformations in the tail, palate, or extremities of the surviving rat and/or mouse fetuses. These findings suggest that the teratogenic properties of N-alkylureas can be categorized into two groups, i.e., mono-alkylated thioureas and methylated ureas or thioureas.
D000014:Abnormalities, Drug-Induced; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects; D008782:Methylurea Compounds / Q000633:toxicity; D051379:Mice; D011247:Pregnancy; D051381:Rats; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity; D014508:Urea / Q000031:analogs & derivatives* / Q000633:toxicity
D008782:Methylurea Compounds; D014508:Urea; D013890:Thiourea